A study of the efficacy and toxicity of isotretinoin as a chemopreventive agent is being continued in a series of eight patients with xeroderma pigmentosum. Initial results identified an improvement of great magnitude in the rate of new skin cancer formation while on high dose therapy. However, high dose therapy was associated with significant toxicity. Patients continut to be evaluated at intermediate doses in an effort to achieve adequate chemoprevention with minimum toxicity and further define the parameters of isotretinoin chemoprevention. One patient had similar benefit on both low and high dose treatment. Four patients had less improvement on low as compared to high dose treatment. This suggests a dose response. One patient had no benefit from high dose isotretinoin and has been started on a study of oral acitretin, an aromatic retinoid. Osteoporosis has been observed in chronic hypervitaminosis A. We had previously identified decreased bone mineral density in a group of etretinate treated patients. We have continued to study retinoid osteoporosis by evaluating bone mineral densities using DEXA scanning, and continue to valuate bone mineral density and parameters of bone turnover. A phase I/II, double-blind study of topical antiflammin, a phospholipase-A2 inhibitor, for the treatment of psoriasis, is in progress. Fourteen patients have been enrolled at three dose levels and enrollment is continuing. Previous projects evaluating the long-term efficacy and toxicity of the retinoids, isotretinoin and etretinate, in the treatment of the skin cancer, disorders of cornification, and psoriasis have been terminated.